Secretion of melatonin by the pineal gland is cyclically stimulated by circadian pacemaker in the hypothalamus and is inhibited by environmental light acting on the pacemaker structure. Thus, plasma melatonin can be used as a biochemical measure of the oscillations of a circadian pacemaker and its interaction with the light-dark cycle to which it is entrained. The pineal is also involved in the recognition of and response to seasonal changes in the environmental photoperiod (dawn-dusk interval). Using a gas chromatographic-mass spectrometric (GC-MS) assay developed in collaboration with Dr. S. Markey of the LCS, Dr. Lewy has investigated circadian rhythms, seasonal rhythms, and sensitivity to light in blind persons and in patients with affective disorders. This year, preliminary findings in both populations have been replicated in a larger number of subjects; we found that (l) the timing of blind persons' melatonin circadian rhythms relative to the day-night cycle is markedly abnormal - in some cases the rhythm is no longer synchronized with the day-night cycle but free-runs according to its own intrinsic 25-hour period. (2) Manic-depressive patients are abnormally sensitive to light. The former finding highlights the importance of light in the homeostasis of circadian rhythm phases and the latter finding suggests a possible cause for circadian rhythm phase disturbances in manic-depressive illness. Because of Dr. Lewy's departure the project will be terminated.